RESUMO
BACKGROUND: Pneumococcal resistance became a global issue during the past decades. Korea is reported to be the hottest spot in the world with regard to the prevalence of penicillin and multidrug resistance. Previous molecular epidemiologic studies strongly suggested that antibiotic-resistant pneumococci from Korea are genetically related. To investigate the molecular characteristics of multidrug-resistant (MDR) pneumococcal isolates in Korea, we performed the DNA sequencing of the gene encoding penicillin-binding protein (PBP) 2B. METHODS: A total of 9 invasive MDR strains which were collected from 1990 to 1995 in various parts of Korea and one internationally epidemic Spanish 23F clone were analyzed. The 1.5 kb transpeptidase-encoding region (TER) of PBP 2B gene was amplified and directly sequenced using ABI PRISM Big Dye Terminator cycle sequencing kit (Perkin Elmer). Sequence data were compared with that of a penicillin-susceptible R6 strain. RESULTS: Alterations in nucleotide sequence (5.4-7.8%) and amino acids (3.0-4.3%) of the PBP 2B gene were relatively uniform among 9 Korean MDR strains. Most alterations in nucleotides (86-94%) and amino acids (86-100%) were noted in the hypervariable region between 408 and 993 bp. All 9 strains possessed 14 common alterations in amino acids, among which Asn-276-->Lys, Arg-285-->Cys and Ser-305-->Phe substitutions were unique to Korean MDR strains. CONCLUSION: Sequence analysis of invasive MDR strains showed that a limited number of amino acid substitutions were noted in the wild-type Korean MDR strains in the transpeptidase domain of the PBP 2B gene. Data strongly suggest the possibility of the spread of a few epidemic clones of resistant pneumococci within Korea, which could partly explain the rapid increase of pneumococcal resistance.